RG100204, A Novel Aquaporin-9 Inhibitor, Reduces Septic Cardiomyopathy and Multiple Organ Failure in Murine Sepsis

• DOI: 10.3389/fimmu.2022.900906
• Publication Date: 2022-06-14T13:49:32Z
• Authors: Shireen Mohammad; Caroline E. O’Rio...; Chiara Verra; Eleonora Aimaretti; Gustavo Ferreira ...; Klaus Dreisch; Johan Evenäs; Patrizia Gena; Angela Tesse; Michael Rützler; Massimo Collino; Giuseppe Calamita; Christoph Thiemer...
• Keywords: Organ dysfunction

Sepsis is caused by systemic infection and a major health concern as it the primary cause of death from infection. It leading mortality worldwide there are no specific effective treatments for sepsis. Gene deletion neutral solute channel Aquaporin 9 (AQP9) normalizes oxidative stress improves survival in bacterial endotoxin induced mouse model In this study we described initial characterization effects novel small molecule AQP9 inhibitor, RG100204, cecal ligation puncture (CLP) polymicrobial vitro , RG100204 blocked H 2 O permeability an ectopic CHO cell expression system abolished LPS increase superoxide anion nitric oxide FaO hepatoma cells. Pre-treatment CLP-mice with (25 mg/kg p.o. before CLP then again at 8 h after CLP) attenuated hypothermia, cardiac dysfunction (systolic diastolic), renal hepatocellular injury CLP-induced Post-treatment also sepsis, but did not significantly reduce liver or hypothermia. The most striking finding was that oral administration late 3 onset sepsis severe Immunoblot quantification demonstrated reduced activation NLRP3 inflammasome pathway. Moreover, myeloperoxidase activity treated lung tissue reduced. Together these results indicate may be drug target